The long term objective of this GESTEC proposal is to achieve three of the primary goals of the Human Genome Project over the next five years: 1. Construct a physical map of the entire human genome at 100 kb average resolution. 2. Develop improved methods for sequencing human genomic DNA and use these methods to obtain DNA sequence of several megabase-sized segments of the human genome. 3. Provide high school students and the general public with information to allow them to make educated decisions concerning personal, ethical, and social questions raised by the work of the Human Genome Project. Projects 1 and 3 will develop 30,000 unique DNA landmarks as Sequence Tagged Sites (STSs) which will serve as the genetic markers for our mapping studies. Project 2 will use radiation hybrid mapping of these STSs to generate a contiguous physical map of the human genome with an average resolution of 100 kb. Since the 30,000 STSs will be designed to span the majority of the estimated 20,000 Sfi 1 sites in the human genome, the 100kb average resolution RH map will be integrated with the Sfi 1 restriction map of the human genome which will be generated by Project 3. Both the Sfi 1 restriction map and the 100kb RH map will provide a foundation for the construction of high resolution clone maps of megabase regions of the human genome (Project 4), which will be sued to develop efficient approaches for sequencing human genomic DNA (Project 5). These five research projects will be supported by a Technical Core and an Administrative Core, as well as by an effective computer database to make our marker, mapping and sequencing data easily available to all researchers (Project 6). Finally, Project 7 will develop a sustained education program to provide large numbers of students, teachers, lay groups and members of the general public with knowledge about the Human Genome Project.